Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) rs10845498 Polymorphism Is Associated with a Decreased Risk of Non-Small Cell Lung Cancer

Objectives: Low-density lipoprotein receptor-related protein 6 (LRP6) modulates Wnt signaling transduction. Altered LRP6 expression leads to abnormal Wnt protein activation, cell proliferation and tumorigenesis. This study investigated the association between LRP6 single-nucleotide polymorphisms (SNPs) and non-small-cell lung cancer (NSCLC) in a Chinese population. Methods: A total of 500 NSCLC patients and 500 healthy controls were recruited for assessment of four LRP6 SNPs using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization-time of flight mass spectrometry. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Results: The frequency of the LRP6 rs10845498 genotype was 60.9% (A/A), 35.5% (AG) and 3.6% (GG) in patients with lung squamous cell carcinoma (SCC) and 69.2% (A/A), 27.2% (A/G) and 3.6% (GG) in controls. Logistic regression analysis revealed that the LRP6 rs10845498 A/A major allele was associated with a reduced risk in developing lung SCC (OR = 0.69; 95% CI, 0.48-1.00; P=0.04), and tobacco smokers had a 2.21 fold greater risk in developing SCC than nonsmokers (p<0.01, 95% CI, 1.72-2.85), and tobacco smokers who carried an “A” allele (AA+AG) in rs6488507 had a 2.34-fold greater risk in developing NSCLC than other patients (p< 0.01, 95%CI, 1.74-3.13). Conclusions: The LRP6 rs10845498 SNP is associated with a reduced risk of lung SCC, while tobacco smoke increases the risk. LRP6 rs6488507 polymorphism synergistically increased the risk of NSCLC in tobacco smokers. Further studies are needed to elucidate the functional impact of LRP6 expression and activity in NSCLC.     

Muscle functional MRI analysis of trunk muscle recruitment during extension exercises in asymptomatic individuals

The present study examined the activity levels of the thoracic and lumbar extensor muscles during different extension exercise modalities in healthy individuals. Therefore, 14 subjects performed four different types of extension exercises in prone position: dynamic trunk extension, dynamic–static trunk extension, dynamic leg extension, and dynamic–static leg extension. Pre‐ and post‐exercise muscle functional magnetic resonance imaging scans from the latissimus dorsi, the thoracic and lumbar parts of the longissimus, iliocostalis, and multifidus were performed. Differences in water relaxation values (T2‐relaxation) before and after exercise were calculated (T2‐shift) as a measure of muscle activity and compared between extension modalities. Linear mixed‐model analysis revealed higher lumbar extensor activity during trunk extension compared with leg extension (T2‐shift of 5.01 ms and 3.55 ms, respectively) and during the dynamic–static exercise performance compared with the dynamic exercise performance (T2‐shift of 4.77 ms and 3.55 ms, respectively). No significant differences in the thoracic extensor activity between the exercises could be demonstrated. During all extension exercises, the latissimus dorsi was the least activated compared with the paraspinal muscles. While all extension exercises are equivalent effective to train the thoracic muscles, trunk extension exercises performed in a dynamic–static way are the most appropriate to enhance lumbar muscle strength.